Is GRM6 p.Pro170Ser (c.508C>T) pathogenic?

GRM6 p.Pro170Ser (c.508C>T) is classified Uncertain significance in GRM6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-01). AlphaMissense: likely pathogenic (0.9745); Very rare (popmax 0.00679%, nfe); Associated with Inborn genetic diseases.

What condition is associated with GRM6 p.Pro170Ser (c.508C>T)?

GRM6 p.Pro170Ser (c.508C>T) is associated with Inborn genetic diseases (ClinVar).

How common is GRM6 p.Pro170Ser (c.508C>T) in the general population?

GRM6 p.Pro170Ser (c.508C>T) is very rare (popmax 0.00679%, nfe) (gnomAD).

What do computational predictors say about GRM6 p.Pro170Ser (c.508C>T)?

AlphaMissense predicts likely pathogenic (score 0.9745) — an in-silico prediction, not a clinical call.

GRM6 p.Pro170Ser

c.508C>T · VCV4032615

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9745 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00679%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9745	likely pathogenic
REVEL	0.934	strongly pathogenic-leaning
SaProt	LLR -14.21	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.42 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 13 kb · p 0.88 · regional, not allelic
Overall
CADD	28.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00679% European (non-Finnish) · 80/1,177,514 alleles

Filtering AF 0.00556% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00515%

Overall 0.00509% 82/1,610,864 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00679%	14,719
Remaining individualsnot grpmax-eligible	0.0032%	31,202

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: GRM6
Protein: p.Pro170Ser
Coding: c.508C>T
MANE Select: NM_000843
Type: single nucleotide variant
Location: chr5:178992080 (GRCh38)
Gene constraint: LOEUF 1.229 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 85.90 · 5 PDB

Full GRM6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GRM6 p.Ala240Pro Uncertain significance ★★ ⚠ same condition
GRM6 p.Ala414Thr Uncertain significance ★★ ⚠ same condition
GRM6 p.Ala421Val Uncertain significance ★★ ⚠ same condition
GRM6 p.Ala432Val Uncertain significance ★★ ⚠ same condition
GRM6 p.Ala466Val Uncertain significance ★★ ⚠ same condition
GRM6 p.Ala482Thr Uncertain significance ★★ ⚠ same condition
GRM6 p.Ala586Thr Uncertain significance ★★ ⚠ same condition
GRM6 p.Arg165Cys Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/grm6-p-pro170ser (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown